The purpose of this study was to investigate the effects of vehicles and organic acids on the in vitro permeation of letrozole across rat skin. Permeation experiments were carried out with 2-chamber diffusion cells through rat skin. The binary solvent mixture of ethanol and isopropyl myristate （IPM） could markedly enhance the cumulative penetrated amount of letrozole after 8 h （Qs） compared with IPM alone, especially the IPM system containing 20% （w/w） ethanol. Surprisingly, the use of complexation with organic acids facilitated skin permeation of letrozole in the IPM--ethanol （20%, w/w） system. Due to different structures of tested organic acids, their effects on the penetration of letrozole were different. This study showed that the addition of an organic acid in the IPM-cthanol （20%, w/w） system was a promising approach to enhance the skin permeability of letrozole.
